Studies in this laboratory are designed to elucidate the role of DNA repair processes in huamn diseases and in carcinogenesis, mutagenesis, and normal and abnormal aging. Most studies have been conducted with cells from patients with xeroderma pigmentosum (XP), all of whom have defective DNA repair plus the clinical abnormalities of multiple cutaneous malignancies and premature aging of sun-exposed skin. Studies are currently being performed on cells from patients with degenerative neurological diseases such as Huntington's disease, ataxia telangiectasia, familial dysautonomia, olivopontocerebellar atrophy, and Cockayne's syndrome. These studies are designed to elucidate the pathogenesis of these disorders as well as to develop presymptomatic (including prenatal) diagnostic tests. We assess the biological effectiveness of DNA repair primarily by in vitro assays of post-irradiation colony-forming ability and trypan blue exclusion. We are extending our work to include cells from patients with other degenerative disorders including Shy-Drager syndrome, idiopathic orthostatic hypotension, retinitis pigmentosa, Usher's syndrome, spinal muscular atrophy, and muscular dystrophy.